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果蝇 USP22/无终止在集体边缘细胞迁移过程中使肌动蛋白细胞骨架极化。

Drosophila USP22/nonstop polarizes the actin cytoskeleton during collective border cell migration.

机构信息

Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.

Department of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.

出版信息

J Cell Biol. 2021 Jul 5;220(7). doi: 10.1083/jcb.202007005. Epub 2021 May 14.

DOI:10.1083/jcb.202007005
PMID:33988679
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8129793/
Abstract

Polarization of the actin cytoskeleton is vital for the collective migration of cells in vivo. During invasive border cell migration in Drosophila, actin polarization is directly controlled by the Hippo signaling complex, which resides at contacts between border cells in the cluster. Here, we identify, in a genetic screen for deubiquitinating enzymes involved in border cell migration, an essential role for nonstop/USP22 in the expression of Hippo pathway components expanded and merlin. Loss of nonstop function consequently leads to a redistribution of F-actin and the polarity determinant Crumbs, loss of polarized actin protrusions, and tumbling of the border cell cluster. Nonstop is a component of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator complex, but SAGA's histone acetyltransferase module, which does not bind to expanded or merlin, is dispensable for migration. Taken together, our results uncover novel roles for SAGA-independent nonstop/USP22 in collective cell migration, which may help guide studies in other systems where USP22 is necessary for cell motility and invasion.

摘要

细胞骨架的极化对于细胞在体内的集体迁移至关重要。在果蝇中侵袭性边缘细胞迁移过程中，肌动蛋白的极化直接受 Hippo 信号复合物的控制，该复合物位于细胞簇中边缘细胞之间的接触处。在这里，我们在参与边缘细胞迁移的去泛素化酶的遗传筛选中发现，非停/USP22 在 Hippo 途径成分扩展和 Merlin 的表达中起着至关重要的作用。非停功能的丧失会导致 F-肌动蛋白和极性决定因子 Crumbs 的重新分布、极化肌动蛋白突起的丧失以及边缘细胞簇的翻滚。非停是 Spt-Ada-Gcn5-乙酰转移酶（SAGA）转录共激活复合物的一个组成部分，但不结合扩展或 Merlin 的 SAGA 的组蛋白乙酰转移酶模块对于迁移是可有可无的。总之，我们的研究结果揭示了 SAGA 非依赖性非停/USP22 在细胞集体迁移中的新作用，这可能有助于指导其他系统的研究，其中 USP22 对于细胞迁移和侵袭是必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/07a25c8ce712/JCB_202007005_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/e64a86a54d3e/JCB_202007005_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/e6275ce23bf9/JCB_202007005_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/b05f6c0c23e7/JCB_202007005_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/b0c7d9220351/JCB_202007005_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/77a1040c235d/JCB_202007005_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/8856bf37d096/JCB_202007005_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/2493d025e90b/JCB_202007005_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/de0655fd12f8/JCB_202007005_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/f4bac9a4fcb7/JCB_202007005_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/07a25c8ce712/JCB_202007005_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/e64a86a54d3e/JCB_202007005_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/e6275ce23bf9/JCB_202007005_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/b05f6c0c23e7/JCB_202007005_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/b0c7d9220351/JCB_202007005_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/77a1040c235d/JCB_202007005_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/8856bf37d096/JCB_202007005_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/2493d025e90b/JCB_202007005_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/de0655fd12f8/JCB_202007005_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/f4bac9a4fcb7/JCB_202007005_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff38/8129793/07a25c8ce712/JCB_202007005_FigS3.jpg

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